|Publication number||US6956205 B2|
|Application number||US 09/882,361|
|Publication date||Oct 18, 2005|
|Filing date||Jun 15, 2001|
|Priority date||Jun 15, 2001|
|Also published as||DE60237742D1, EP1267387A2, EP1267387A3, EP1267387B1, US20040149902|
|Publication number||09882361, 882361, US 6956205 B2, US 6956205B2, US-B2-6956205, US6956205 B2, US6956205B2|
|Inventors||Melvin A. Park|
|Original Assignee||Bruker Daltonics, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (34), Non-Patent Citations (3), Referenced by (37), Classifications (9), Legal Events (7)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to a method and apparatus for the injection of ions into a mass spectrometer for subsequent analysis. An apparatus for use in an ion source having an ion production means and an ion guide is described which facilitates the transmission of ions from an elevated pressure ion production region to a reduced pressure ion analysis region of a mass spectrometer for mass analysis. Specifically, a preferred embodiment of the present invention allows a multitude of ion production means to simultaneously introduce ions into a single ion guide and transmit the ions to a mass analyzer.
The present invention relates to multipole ion guides for use in mass spectrometry. The apparatus and methods for ionization described herein are enhancements of the techniques that are referred to in the literature relating to mass spectrometry—an important tool in the analysis of a wide range of chemical compounds. Specifically, mass spectrometers can be used to determine the molecular weight of sample compounds. The analysis of samples by mass spectrometry consists of three main steps—formation of gas phase ions from sample material, mass analysis of the ions to separate the ions from one another according to ion mass, and detection of the ions. A variety of means and methods exist in the field of mass spectrometry to perform each of these three functions. The particular combination of the means and methods used in a given mass spectrometer determine the characteristics of that instrument.
To mass analyze ions, for example, one might use magnetic (B) or electrostatic (E) analysis. Ions passing through a magnetic or electrostatic field will follow a curved path. In a magnetic field the curvature of the path will be indicative of the momentum-to-charge ratio of the ion. In an electrostatic field, the curvature of the path will be indicative of the energy-to-charge ratio of the ion. If magnetic and electrostatic analyzers are used consecutively, then both the momentum-to-charge and energy-to-charge ratios of the ions will be known and the mass of the ion will thereby be determined. Other mass analyzers are the quadrupole (Q), the ion cyclotron resonance (ICR), the time-of-flight (TOF), and the quadrupole ion trap analyzers. The analyzer which accepts ions from the ion guide described here may be any of a variety of these.
Before mass analysis can begin, however, gas phase ions must be formed from sample material. If the sample material is sufficiently volatile, ions may be formed by electron ionization (EI) or chemical ionization (CI) of the gas phase sample molecules. For solid samples (e.g., semiconductors, or crystallized materials), ions can be formed by desorption and ionization of sample molecules by bombardment with high energy particles. Secondary ion mass spectrometry (SIMS) , for example, uses keV ions to desorb and ionize sample material. In the SIMS process a large amount of energy is deposited in the analyte molecules. As a result, fragile molecules will be fragmented. This fragmentation is undesirable in that information regarding the original composition of the sample (e.g., the molecular weight of sample molecules) will be lost.
For more labile, fragile molecules, other ionization methods now exist. The plasma desorption (PD) technique was introduced by Macfarlane et al. in 1974 (Macfarlane, R. D.; Skowronski, R. P.; Torgerson, D. F., Biochem. Biophys. Res Commoun. 60 (1974) 616). Macfarlane et al. discovered that the impact of high energy (MeV) ions on a surface, like SIMS would cause desorption and ionization of small analyte molecules. However, unlike SIMS, the PD process results also in the desorption of larger, more labile species (e.g., insulin and other protein molecules).
Lasers have been used in a similar manner to induce desorption of biological or other labile molecules. See, for example, VanBreeman, R. B.: Snow, M.: Cotter, R. J., Int. J. Mass Spectrom. Ion Phys. 49 (1983) 35; Tabet, J. C.; Cotter, R. J., Anal. Chem. 56 (1984) 1662; or Olthoff, J. K.; Lys, I.: Demirev, P.: Cotter, R. J., Anal. Instrument. 16 (1987) 93. Cotter et al. modified a CVC 2000 time-of-flight mass spectrometer for infrared laser desorption of involatile biomolecules, using a Tachisto (Needham, Mass.) model 215G pulsed carbon dioxide laser. The plasma or laser desorption and ionization of labile molecules relies on the deposition of little or no energy in the analyte molecules of interest. The use of lasers to desorb and ionize labile molecules intact was enhanced by the introduction of matrix assisted laser desorption ionization (MALDI) (Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshica, T., Rapid Commun. Mass Spectrom. 2 (1988) 151 and Karas, M.; Hillenkamp, F., Anal. Chem. 60 (1988) 2299). In the MALDI process, an analyte is dissolved in a solid, organic matrix. Laser light of a wavelength that is absorbed by the solid matrix but not by the analyte is used to excite the sample. Thus, the matrix is excited directly by the laser, and the excited matrix sublimes into the gas phase carrying with it the analyte molecules. The analyte molecules are then ionized by proton, electron, or cation transfer from the matrix molecules to the analyte molecules. This process, MALDI, is typically used in conjunction with time-of-flight mass spectrometry (TOFMS) and can be used to measure the molecular weights of proteins in excess of 100,000 daltons.
Atmospheric pressure ionization (API) includes a number of methods. Typically, analyte ions are produced from liquid solution at atmospheric pressure. One of the more widely used methods, known as electrospray ionization (ESI), was first suggested by Dole et al. (M. Dole, L. L. Mack, R. L. Hines, R. C. Mobley, L. D. Ferguson, M. B. Alice, J. Chem. Phys. 49, 2240, 1968). In the electrospray technique, analyte is dissolved in a liquid solution and sprayed from a needle. The spray is induced by the application of a potential difference between the needle and a counter electrode. The spray results in the formation of fine, charged droplets of solution containing analyte molecules. In the gas phase, the solvent evaporates leaving behind charged, gas phase, analyte ions. Very large ions can be formed in this way. Ions as large as 1 MDa have been detected by ESI in conjunction with mass spectrometry (ESMS).
In addition to ESI, any other ion production method that can be adapted to atmospheric pressure might be used. For example, MALDI has recently been adapted by Victor Laiko and Alma Burlingame to work at atmospheric pressure (Atmospheric Pressure Matrix Assisted Laser Desorption Ionization, poster #1121, 4th International Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, Aug. 25-29, 1998) and by Standing et al. at elevated pressures (Time of Flight Mass Spectrometry of Biomolecules with Orthogonal Injection+Collisional Cooling, poster #1272, 4th International Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, Aug. 25-29, 1998; and Orthogonal Injection TOFMS Anal. Chem. 71(13), 452A (1999)). The benefit of adapting ion sources in this manner is that the ion optics and mass spectral results are largely independent of the ion production method used.
An elevated pressure ion source always has an ion production region (wherein ions are produced) and an ion transfer region (wherein ions are transferred through differential pumping stages and into the mass analyzer). The ion production region is at an elevated pressure—most often atmospheric pressure—with respect to the analyzer. The ion production region will often include an ionization “chamber” (e.g.
Once the ions are produced, they must be transported to the vacuum for mass analysis. Generally, mass spectrometers (MS) operate in a vacuum between 10−4 and 10−10 torr depending on the type of mass analyzer used. In order for the gas phase ions to enter the mass analyzer, they must be separated from the background gas carrying the ions and transported through the single or multiple vacuum stages.
The use of multipole ion guides has been shown to be an effective means of transporting ions through a vacuum system. Publications by Olivers et al. (Anal. Chem, Vol. 59, p. 1230-1232, 1987), Smith et al. (Anal. Chem. Vol. 60, p. 436-441, 1988) and Douglas et al. U.S. Pat. No. 4,963,736 (Douglas) have reported the use of AC-only quadrupole ion guides to transport ions from an API source to a mass analyzer. Such multipole ion guides may be configured as collision cells capable of being operated in RF only mode with a variable DC offset potential applied to all rods. Thomson et al., U.S. Pat. No. 5,847,386 (Thomson) also describes a quadrupole ion guide. The ion guide of Thomson is configured to create a DC axial field along its axis to move ions axially through a collision cell, inter alia, or to promote dissociation of ions (i.e., by Collision Induced Dissociation (CID)).
Other schemes are available utilizing both RF and DC potentials in order to facilitate the transmission of ions of a certain range of m/z values. For example, in H. R. Morris et al., High Sensitivity Collisionally Activated Decomposition Tandem Mass Spectrometry on a Novel Quadrupole/Orthogonal Acceleration Time-of-Flight Mass Spectrometer, Rapid Commun. Mass Spectrom. 10, 889 (1996) (Morris), uses a series of multipoles in their design, one of which is a quadrupole which is capable of being operated in a “wide bandpass” mode or a “narrow bandpass” mode. In the wide bandpass mode, an RF-only potential is applied to the quadrupole and ions of a relatively broad range of m/z values are transmitted. In narrow bandpass mode both RF and DC potentials are applied to the quadrupole such that ions of only a narrow range of m/z values are selected for transmission through the quadrupole. In subsequent multipoles the selected ions may be activated towards dissociation. In this way, the instrument of Morris is able to perform MS/MS experiments with the first mass analysis and subsequent fragmentation occurring in what would otherwise be simply a set of multipole ion guides.
Further, mass spectrometers similar to that of Whitehouse et al. U.S. Pat. No. 5,652,427 (Whitehouse), entitled “Multipole Ion Guide for Mass Spectrometry”, use multipole RF ion guides to transfer ions from one pressure region to another in a differentially pumped system. In the source of Whitehouse, ions are produced by ESI or APCI at substantially atmospheric pressure. These ions are transferred from atmospheric pressure to a first differential pumping region by the gas flow through a glass capillary. Ions are transferred from this first pumping region to a second pumping region through a “skimmer” by an electric field between these regions as well as gas flow. A multipole in the second differentially pumped region accepts ions and guides them through a restriction and into a third differentially pumped region. This is accomplished by applying AC and DC voltages to the individual poles.
A four vacuum stage ES/MS quadrupole mass spectrometer according to Whitehouse, incorporating a multipole ion guide beginning in one vacuum pumping stage and extending contiguously into an adjacent pumping stage, is depicted in FIG. 2. As discussed above, ions are formed from sample solution by an electrospray process when a potential is applied between spray needle 27 of sprayer 26 and sampling orifice 38. According to the prior art system shown in
In the scheme of Whitehouse, an RF only potential is applied to multipole ion guide 42. As a result, ion guide 42 is not “selective” but rather transmits ions over a broad range of mass-to-charge (m/z) ratios. Such a range as provided by prior art multipoles is inadequate for certain applications, such as for Matrix Assisted Laser Desorption/Ionization (MALDI), because the ions produced may be well out of this m/z range. In other words, high m/z ions such as are often produced by the MALDI ionization method are often out of the range of transmission of conventional multipole ion guides.
Thus, electric voltages usually applied to the conventional ion guide are used to transmit ions from an entrance end to an exit end. Analyte ions produced in the ion production region pass through a capillary or other ion transfer device to move the ions to a differentially pumped region and enter the ion guide at the entrance end. Through collisions with gas in the ion guide, the kinetic energy of the ions is reduced to thermal energies. Simultaneously, the RF potential on the poles of the ion guide forces ions to the axis of the ion guide. Then, ions migrate through the ion guide toward its exit end, where the ions typically either enter a second ion guide or enter the mass analysis region.
Whitehouse also discloses use of two or more ion guides in consecutive vacuum pumping stages to allow different DC and RF values. However, losses in ion transmission efficiency may occur in the region of static voltage lenses between ion guides. For example, a commercially available API/MS instrument manufactured by Hewlett Packard incorporates two skimmers and an ion guide. The drag stage of a conventional turbo pump is used to pump the region between the skimmers. That is, an additional pumping stage/region is added without the addition of an extra turbo pump, and therefore, improved pumping efficiency may be achieved. In this dual skimmer design, there is no ion focusing device between skimmers, therefore ion losses may occur as the gases are pumped away. A second example is demonstrated by a commercially available API/MS instrument manufactured by Finnigan which applies an electrical static lens between capillary and skimmer to focus the ion beam. Due to narrow mass range of the static lens, the instrument may need to scan the voltage to optimize the ion transmission.
In addition, the electrode rods of the prior art multipole ion guides described above are positioned in parallel and are equally spaced at a common radius from the centerline of the ion guide. Thus, ions with a m/z ratio falling within the ion guide stability window established by the applied voltages have stable trajectories within the ion guide's internal volume bounded by the parallel, evenly spaced rods. This is true for quadrupoles, hexapoles, etc. For example,
During operation, DC potentials are applied to each of skimmer 84 and gate electrode 89 of multipole ion guide 88 (shown is a hexapole). At skimmer 84 (i.e., entrance end 92 of ion guide 88), ions pass from an ion source region (not shown) through electrically conducting skimmer 84 into the region between the parallel conducting rods 86. In other words, the DC potential applied to skimmer 84 is set such that the ions are focused into ion guide 88. Next, a high voltage RF potential is applied to conducting rods 86 of ion guide 88 to “force” the ions (or focus the ions) to centerline 90 (or axis) of the ion guide. In addition, a collisional gas has been used within such ion guides to collisionally cool the ions therein. Next, the ions will migrate toward exit end 94 of ion guide 88, and at exit end 94 gate electrode 89 is positioned such that a repulsive DC potential may be applied to trap the ions within ion guide 88 until it is time to analyze the ions. On the other hand, when a non-repulsive DC potential is applied to gate electrode 89, the ions may pass freely out of ion guide 88 and into a mass analyzer.
In sum, previous ion guides (e.g., quadrupoles, hexapoles, etc.) have comprised parallel conducting rods evenly spaced from a centerline, having DC electrodes positioned at their entrance and exit ends, and high voltage RF and DC potentials are applied thereto to focus, transmit, and/or trap ions. It has been observed that such ion guides are limited in their applications. Specifically, such conventional ion guides may only accept ions from a single ion production means and changing from one ion production means to another is cumbersome and time consuming. In addition, prior art ion guides are often inadequate for transmission of ions produced by the MALDI method, as these ions are often of a m/z range out of the range for which the ion guides are capable. Yet another disadvantage of prior art ion guides is their limited use for mass selection and performing chemical reactions. As discussed below, the ion guide of the present invention overcomes these limitations and/or deficiencies in conventional ion guides.
The present invention provides an ion guide for use in a mass spectrometer to facilitate the transmission of ions from an elevated pressure ion production region to a reduced pressure ion analysis region. It is one aspect of the invention to utilize multiple ion production means simultaneously to transmit ions into an analyzer. It is another aspect of the invention that embodiments can be interfaced to atmospheric pressure ion sources, including Electrospray (ESI) and electron ionization/chemical ionization (EI/CI). Embodiments of the present invention can be configured in any variety of hyphenated or non-hyphenated analyzer.
The invention, as described below, includes a number of embodiments. For instance, the invention can be applied to multipole ion guides with any number of poles, and any geometry. It can utilize multiple ion production means of many different types at the same time, and does not even need to accept ions directly from the ion production means. Also, the analyzer may be any of a variety of hyphenated or non-hyphenated analyzers. The ion guide is positioned between the ion production means and the mass analyzer. However, the ion guide does not need to accept ions directly from the ion production means. In another embodiment of the invention, ions may pass through some other device before entering the ion guide. For example, ions might be produced by an ESI ion production means and be analyzed by ion mobility spectroscopy before entering the ion guide. In the preferred embodiment of the invention as shown in
In the preferred embodiment of the invention, though, the ion guide need not be planar in cross section as shown in FIG. 4B. Rather, the rods could be arranged to form arcs, or any other useful geometry. Also, the rods could be assembled as a metal deposition (e.g., a vapor deposition) on the insulator. For example, rods might be formed as a gold vapor deposit on two substantially planar ceramic plates. In such a preferred embodiment, the ceramic plates might be produced, for example, with threaded mounting holes such that the plates can be mounted adjacent to one another in an instrument. The ceramic plates might also have vent holes for allowing gas within the ion guide to pass out of the ion guide and into a pump.
As shown in
The analyzer which accepts ions from the ion guide may also be of a variety of analyzers. These may be hyphenated or non-hyphenated analyzers—e.g., a time-of-flight mass analyzer (TOFMS), a quadrupole, a quadrupole ion trap, a Fourier transform ion cyclotron resonance mass analyzer (FT-ICRMS), or an ion mobility spectrometer (IMS).
The multipole ion guide is configured to perform many functions including, but not limited to m/z selection, trapping and subsequent ion fragmentation using collision induced dissociation (CID) within the multipole ion guide. Ion selection by m/z is possible by adjusting the DC and RF potentials and the RF frequency on the rods. Gas phase chemical reactions can also be carried out in the invention described. For example, ESI ions may be trapped in the ion guide, and then neutral reactant gas leaked into the guide.
In the present invention, multipole ion guides are configured so that ions from a multitude of ion production means can simultaneously be introduced into a single ion guide and transmitted into an analyzer. The ion guide described here can be configured with four (quadrupole), six (hexapole), eight (octapole) or more rods or poles. It is not required that there be a specific entrance point. Rather, there can be a multitude of entrances. Because the present invention allows for a multitude of entrances, a multitude of ion production means can be used simultaneously.
Other objects, features, and characteristics of the present invention, as well as the methods of operation and functions of the related elements of the structure, and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following detailed description with reference to the accompanying drawings, all of which form a part of this specification.
A further understanding of the present invention can be obtained by reference to a preferred embodiment set forth in the illustrations of the accompanying drawings. Although the illustrated embodiment is merely exemplary of systems for carrying out the present invention, both the organization and method of operation of the invention, in general, together with further objectives and advantages thereof, may be more easily understood by reference to the drawings and the following description. The drawings are not intended to limit the scope of this invention, which is set forth with particularity in the claims as appended or as subsequently amended, but merely to clarify and exemplify the invention.
For a more complete understanding of the present invention, reference is now made to the following drawings in which:
As required, a detailed illustrative embodiment of the present invention is disclosed herein. However, techniques, systems and operating structures in accordance with the present invention may be embodied in a wide variety of forms and modes, some of which may be quite different from those in the disclosed embodiment. Consequently, the specific structural and functional details disclosed herein are merely representative, yet in that regard, they are deemed to afford the best embodiment for purposes of disclosure and to provide a basis for the claims herein which define the scope of the present invention. The following presents a detailed description of a preferred embodiment (as well as some alternative embodiments) of the present invention.
Referring first to
Similarly, ion guide 100 is capped longitudinally on its top and bottom by capping electrodes 104 and 105, respectively. Again, capping electrodes 104 and 105 are substantially planar (or flat) conductive electrodes, but because conducting rods 102 are preferably of different lengths, having a first end approximately in a single plane, ion guide 100 preferably has conducting rods 102 forming a second end not in a single plane. That is, conducting rods 102 at the center of ion guide 100 are preferably longest, with conducting rods 102 progressively getting shorter towards the top and bottom edges of ion guide 100. Preferably, conducting rods 102 are of such lengths that when positioned in parallel, a side view of ion guide 100 depicts the second end of rods 102 forming a generally semicircular shape. In such an embodiment, top and bottom capping electrode 104 has a generally curved portion which conforms to the shape of the second end of ion guide 100 formed by conducting rods 102. Of course, top and bottom capping electrode 104 is such that opening 106 remains at the second end of ion guide 100 for introduction of the ions into ion guide 100. Specifically, the entrance end of ion guide 100, top and bottom capping electrode 104 extends continuously around the second end of conducting rods 102.
For example, sample ions enter ion guide 100 through aperture (or opening) 106 and exit ion guide 100 through exit electrode 108. Preferably, high voltage RF potentials are applied between conducting rods 102, with top and bottom capping electrode 104 being held at a repulsive DC potential to “force” the ions toward the center of ion guide 100. As shown in
Turning next to
Referring next to
For example, sample ions enter ion guide 120 through aperture (or opening) 122 and exit ion guide 120 through exit electrode 134. Preferably, high voltage RF potentials are applied to conducting rods 132, with top and bottom capping electrode 130 being held at a repulsive DC potential to “force” the ions toward the center of ion guide 120.
First, regarding ESI ion production means 118, the ions enter ion guide 120 through aperture 122 in capping electrode 130. As with conventional ESI, sample solution is sprayed from a sprayer (not shown) such that a spray of fine droplets of sample solution exits a spray needle (not shown) of the sprayer. Due to an electrical potential between the spray needle and the entrance end (not shown) of capillary 118, the fine droplets of sample solution are ionized. The formed analyte ions then enter capillary 118 through an opening in the entrance end, and the ions are transported through a channel within capillary 118 to exit end 117 of capillary 118. Upon exiting capillary 118, the ions 119 may enter ion guide 120 through aperture 122. As described above, a flow of neutral gas may be used to aid or guide the ions into ion guide 120 through aperture 122. Optionally, as shown in
Second, with respect to EI/CI ion production means 112, sample ions may enter ion guide 120 through aperture 124. As shown, aperture 124 is positioned at an angle with respect to conducting rods 132 of ion guide 120. Optionally, EI/CI source may be positioned at aperture 122 in place of ESI source 118, or alternatively at aperture 126 in place of the MALDI laser 114.
Third, regarding MALDI ion production means 114/116, ions are introduced into ion guide 120 through aperture 128 when MALDI sample 116 is struck by MALDI Laser 117. The laser light passes through ion guide 120 after entering at aperture 126 and exits through aperture 128. Upon exiting aperture 128, laser beam 114 strikes MALDI sample surface 116 thereby generating sample ions which pass into ion guide 120 through aperture 128.
With each of these ionization methods, capping electrode 130 maintains a repulsive DC potential, as does gate electrode 137 at the exit end of ion guide 120. Of course, it is consistent with the invention that other types of ionization methods may be used (e.g., atmospheric pressure chemical ionization, plasma desorption, glow discharge, secondary ionization, fast atom bombardment, etc.). Also, in accordance with the invention, ions need not be accepted directly from an ion production means. Rather, ions may pass through some other device before entering the ion guide. For example, ions might be produced by an ESI source and be analyzed by ion mobility spectroscopy before entering the ion guide. Alternatively, ions may pass through a capillary device before entering the ion guide.
Turning next to
An alternate embodiment (not shown) of ion guide 120 comprises multiple capping electrodes. That is, capping electrode 130 as shown in
Next, as with
Turning now to
During operation, ions may be generated from an API source (e.g., ESI or APCI) (not shown), and are introduced into first differential pumping stage 145 through an ion transport device such as a capillary. First pumping stage 145 may be pumped to a pressure lower than atmospheric pressure, for example, to a pressure of approximately 1-2 mbar. The transported ions in first pumping stage 145 are directed by an electric field into orifice 152 of first skimmer 150 and into multipole ion guide assembly 140. The electric field may be generated by application of a potential difference across , for example, a capillary's exit end and first skimmer 150. This electric field is applied such that the ions are directed toward orifice 152 of first skimmer 150, while neutral gas particles are pumped away. Optionally, this electric field may be varied depending on the desired result, the size of the ions being directed, the distance between a capillary exit end and first skimmer 150, etc. Alternatively, it is envisioned that in certain situations better results may be obtained without application of an electric field across the capillary exit end and first skimmer 150. Optionally, o-ring seals 158 may be used to provide a lateral seal between pressure regions.
The ions which pass through orifice 152 of skimmer 150 then enter a second differential pumping stage, which is further pumped by a vacuum pump (e.g., a turbo molecular drag pump). This second pumping stage may be pumped and maintained at a pressure in the range from 1×10−2 mbar to 1×10−1 mbar. At this point, the surviving ions enter pre-multipole 144, which may be operated as an RF only ion guide, wherein the ions are further separated from any neutral gas molecules. Pre-multipole 144 may comprise a plurality of electrode rods, each having a potential applied thereto such that the resulting electric field “pushes” or forces the ions toward a central axis as the ions continue to move through pre-multipole 144 toward a second skimmer 148 (which leads to yet another pumping stage). The ions then pass through second skimmer 148, while the neutral gas molecules, which are not affected by the electrical field, are pumped away. In one configuration, pre-multipole 144 is positioned between first skimmer 150 and second skimmer 148, and is located entirely in a second differential pumping stage. Of course, alternative configurations may be used. For example, pre-multipole 144 may be positioned to cross from one pumping stage to another, one or both skimmers may be removed, or one or both skimmers may be replaced with focusing lenses (e.g., Einsel lenses, etc.).
As the ions pass through second skimmer 148, they enter yet another (third) pumping stage and multipole 146. This third pumping stage may be pumped to and maintained at a pressure in the range from 1×10−3 mbar to 1×10−2 mbar. At this point, the surviving ions enter multipole 146, which may be operated as an RF only ion guide, wherein the ions are further separated from any neutral gas molecules. As described in co-pending application Ser. No. 09/636,321, multipole 146 may comprise a plurality of electrodes, each having an electric potential applied thereto such that the resulting electric field “pushes” or forces the ions toward a central axis of multipole 146. Again, application of the electric field may separate the ions from other neutral gas molecules present (which are pumped away because they are not affected by the electrical field). That is, neutral gas molecules will be continuously pumped away by the connected pump (not shown) (e.g., a turbo molecular drag pump). In addition, the introduction or presence of collisional gas into the third pumping stage results in the collisional cooling of the ions within multipole 146 as the ions are being “guided” therethrough. The cooled ions then pass through exit electrodes 156 as they are introduced into mass analysis region 155 for subsequent mass analysis. Mass analysis region 155 may comprise any of a number of mass analysis devices, including but not limited to time-of-flight (TOF), quadrupole (Q), Fourier transform ion cyclotron resonance (FTICR), magnetic (B), electrostatic (E) or quadrupole ion trap analyzers.
In an embodiment of the multipole ion guide assembly 140 (as described in co-pending application Ser. No. 09/636,321, multipole 146 is positioned between second skimmer 148 and exit electrodes 156 (which lead to mass analysis stage 155), with multipole 146 being positioned within the third pumping stage. Of course, alternate configurations are described, such as, multipole 146 being positioned across multiple pumping stages, skimmer 148 or exit electrodes 156 being removed or replaced by other elements such as focusing lenses (e.g., Einsel lenses, etc.).
In addition, the preferred embodiment of multipole ion guide assembly 140 (as set forth in co-pending application Ser. No. 09/636,321) includes pre-multipole 144 positioned between first and second skimmers (150 & 148, respectively) to separate the ions from any existing neutral gas molecules prior to the ions entering multipole 146. In addition, pre-multipole 144 may focus ions onto the center of second skimmer 148 while the neutral gas molecules are pumped away. Efficient differential pumping in the pumping stages allows multipole 146 (the main ion guide) to be in a pressure region having a pressure which is both low enough for ion trapping and high enough for collisional cooling. Multipole ion guide assembly 140 may be used in applications requiring either ion trapping (for a specific period of time), ion selecting, ion fragmenting, etc. For instance, if the pressure in the region containing multipole 146 is too high, ions may be scattered or fragmented. In a single skimmer system, the effects of this scattering or fragmenting are difficult to manage. The presence of more than one skimmer along with short pre-multipole 144 minimizes scattering and fragmentation of the sample ions.
Also as shown, multipole ion guide assembly 140 may comprise housing 142 in which first skimmer 150, second skimmer 148, pre-multipole 144, multipole 146, and exit electrodes 156 are all secured in longitudinal alignment. These ion optic elements are all maintained in longitudinal alignment with each other such that ions may be transported on a single axis through each optical component of multipole ion guide assembly 140 from the ion production region (or first pumping region 145) to the mass analyzer in mass analysis region 155. Housing 142 may be made from any rigid and durable material, such as aluminum.
Within housing 142, skimmers 150 and 148, pre-multipole 144, multipole 146 and exit electrodes 156 all may be secured by insulating holders. These insulating holders may provide electrical insulation for each component from housing 142, as well as from each other. In addition, these insulating holders secure skimmers 150, 148, pre-multipole 144, multipole 146 and exit electrodes 156 all in longitudinal alignment within housing 142.
During operation of multipole ion guide assembly 140, as shown in
Once transported through pre-multipole 144, the sample ions are introduced through orifice 154 of skimmer 148 (as discussed above) and into a second pumping stage and multipole 146. While in multipole 146, the ions are further separated from any existing neutral gas molecules, are trapped, collisionally cooled, selected, fragmented, scattered, etc. (as discussed above), and are transported longitudinally therethrough. At the exit end of multipole 146, the selected (or fragmented, etc.) sample ions pass through exit electrodes 156 where the ions may be accelerated into a mass analyzer for subsequent analysis.
Regarding multipole ion guide assembly 140 shown in
Referring next to
Similar to that described above for
During operation, ions may be generated from an API ion production means (e.g., ESI or APCI) (not shown), and are introduced into first differential pumping region 204 through an ion transport device such as a capillary. Alternatively, ions may enter region 204 directly from an ion production means. This first region 204 is preferably pumped to a pressure lower than atmospheric pressure by vacuum pump 218—for example, region 204 may be pumped to a pressure of approximately 1-2 mbar. Once within region 204, the transported ions are directed by an electric field into orifice 210 of first skimmer 186 and into multipole ion guide assembly 200. The electric field may be generated by application of a potential difference across, for example, capillary exit end 184 and first skimmer 186. Alternatively, the electric field may be generated by application of a potential difference across an ion source (e.g., a spray needle) and first skimmer 186. This electric field may be applied such that the ions are directed toward orifice 210 of first skimmer 186, while neutral gas particles are pumped away. Optionally, this electric field may be varied depending on the desired result, the size of the ions being directed, the distance between capillary exit 184 (or some other element) and first skimmer 186, etc. Alternatively, it is envisioned that in certain situations better results may be obtained without application of the electric field across capillary exit 184 and first skimmer 186.
The ions that pass through first skimmer 186 then enter second differential pumping region 206, which is further pumped by vacuum pump 219 (e.g., a turbo molecular drag pump) to a lower pressure region, preferably, in the range from 1×10−2 mbar to 1×10−1 mbar. Here, the surviving ions may enter pre-multipole 188, preferably operated as an RF only ion guide, wherein the ions are further separated from any neutral gas molecules. The preferred embodiment of pre-multipole 188 is described fully in co-pending application Ser. No. 09/636,321, which is herein incorporated by reference. Generally, though, pre-multipole 188 comprises a plurality of electrode rods, each having a potential applied thereto such that the resulting electric field “pushes” or “forces” the ions toward a central axis as the ions continue to move through pre-multipole 188 toward orifice 198 of skimmer 196 (which leads to yet another pumping region).
The ions then pass through second skimmer 196, while the neutral gas molecules, which are not affected by the electrical field, are pumped away. In the preferred embodiment, pre-multipole 188 is positioned between first skimmer 186 and second skimmer 196, and is located entirely in first differential pumping region 204. Of course, alternative arrangements may be used. For example, pre-multipole 188 may be positioned to cross from one pumping stage to another (i.e., from first pumping region 204 into second pumping region 206), one or both skimmers may be removed, or one or both skimmers may be replaced with focusing lenses (e.g., Einsel lenses, etc.).
Once through orifice 198 of second skimmer 196, the ions preferably enter third pumping region 208 where they also enter RF-DC ion guide 193. Preferably, this third pumping region 208 is pumped to and maintained at a pressure in the range from 1×10−3 mbar to 1×10−2 mbar. Here, the surviving ions enter ion guide 193, preferably operated as an RF-DC ion guide, wherein the ions are further separated from any neutral gas molecules. As described herein above with respect to
Preferably, conducting rods 194 are of such lengths that when positioned in parallel, a side view of ion guide 193 (as shown in
During operation, sample ions enter ion guide 193 through orifice 198 of skimmer 196 and exit ion guide 193 through exit electrodes 212. Preferably, high voltage RF potentials are applied between conducting rods 194, with top and bottom capping electrode 192 being held at a repulsive DC potential to “force” the ions toward the central axis (i.e., the longitudinal axis) of ion guide 193. Application of the electric field separates the ions from other neutral gas molecules present (which are pumped away because they are not affected by the electrical field). That is, neutral gas molecules will be continuously pumped away by vacuum pump 217 (not shown) (e.g., a turbo molecular drag pump). In addition, the introduction (or presence) of collisional gas in third pumping region 208 (i.e., where ion guide 193 is located) results in the collisional cooling of the ions within ion guide 193 as the ions are being “guided” therethrough. The cooled ions then pass through exit electrodes 212 as they are introduced into mass analysis region 202 for subsequent mass analysis. Mass analysis region 202 may comprise any of a number of mass analysis devices, including but not limited to time-of-flight (TOF), quadrupole (Q), Fourier transform ion cyclotron resonance (FTICR), magnetic (B), electrostatic (E), or quadrupole ion trap analyzers.
In the preferred embodiment of the invention, ion guide 193 is positioned between second skimmer 196 and exit electrodes 212 (which lead to mass analysis region 202), with ion guide 193 being entirely positioned within a single pumping region (here it is the third region). Of course, alternative configurations may be used, including but not limited to, for example, ion guide 193 being positioned across multiple pumping stages, skimmer 196 or exit electrodes 212 being removed or replaced by other elements such as focusing lenses (e.g., Einsel lenses, etc.), etc.
As demonstrated in
Also as shown in
Within housing 190, skimmers 186 & 196, pre-multipole 188, multipole 193 and exit electrodes 212 are all preferably secured in longitudinal alignment by insulating holders (not shown). These insulating holders preferably provide electrical insulation for each component from housing 190, as well as from each other.
In a preferred operation of multipole ion guide assembly 200 as shown in
After passing through pre-multipole 188, ions are introduced through skimmer 196 (as discussed above) into second pumping region 206 and ion guide 193. As previously described herein regarding
In multipole ion guide assembly 200, which incorporates the preferred embodiment of ion guide 193 according to the present invention, as shown in
While the present invention has been described with reference to one or more preferred embodiments, such embodiments are merely exemplary and are not intended to be limiting or represent an exhaustive enumeration of all aspects of the invention. The scope of the invention, therefore, shall be defined solely by the following claims. Further, it will be apparent to those of skill in the art that numerous changes may be made in such details without departing from the spirit and the principles of the invention. It should be appreciated that the present invention is capable of being embodied in other forms without departing from its essential characteristics.
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|U.S. Classification||250/288, 250/282, 250/281, 250/292|
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|Mar 5, 2002||AS||Assignment|
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